tbuckley/cabot-search huggingface dataset:
Selective and replicable neuroimaging-based indicators of pain discriminability
Authors: Li-Bo Zhang, Xue-Jing Lu, Gan Huang, Hui-Juan Zhang, Yi-Heng Tu, Ya-Zhuo Kong, Li Hu
Journal: Cell Reports Medicine (2022)

Neural indicators of pain discriminability have far-reaching theoretical and clinical implications but have been largely overlooked previously. Here, to directly identify the neural basis of pain discriminability, we apply signal detection theory to three EEG (Datasets 1–3, total N = 366) and two fMRI (Datasets 4–5, total N = 399) datasets where participants receive transient stimuli of four sensory modalities (pain, touch, audition, and vision) and two intensities (high and low) and report perceptual ratings. Datasets 1 and 4 are used for exploration and others for validation. We find that most pain-evoked EEG and fMRI brain responses robustly encode pain discriminability, which is well replicated in validation datasets. The neural indicators are also pain selective since they cannot track tactile, auditory, or visual discriminability, even though perceptual ratings and sensory discriminability are well matched between modalities. Overall, we provide compelling evidence that pain-evoked brain responses can serve as replicable and selective neural indicators of pain discriminability.
Anti-CD73 antibody activates human B cells, enhances humoral responses and induces redistribution of B cells in patients with cancer
Authors: Richard A Miller, Jason John Luke, Shenshen Hu, Suresh Mahabhashyam, William B Jones, Thomas Marron, Jaime R Merchan, Brett G M Hughes, Stephen B Willingham
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background CD73 is widely expressed on immune cells playing a critical role in immunomodulatory functions including cell adhesion and migration, as a costimulatory molecule for T cells and in production of adenosine. The function of CD73 expressed on B cells has not been fully characterized. Mupadolimab is an anti-human CD73 antibody that activates B cells. We evaluated the characteristics of this antibody and its effects on immune cells in vitro and in vivo. Methods Mupadolimab binding to CD73, inhibition of CD73 enzymatic activity, and effects on lymphocyte activation were evaluated in vitro by measuring changes in immunophenotype by flow cytometry. Cryogenic-transmission electron microscopy was used to determine epitope binding. Effects on human B cells in vivo were evaluated in immunodeficient NSG-SGM3 mice immunized with SARS-CoV-2 and influenza viral antigens. Safety and immune effects were evaluated in the completed dose escalation portion of a phase 1 trial conducted in patients with cancer. Results Mupadolimab binds to a unique epitope on CD73 POS B cells resulting in their activation and differentiation through B cell receptor signaling pathways. Mupadolimab induces expression of CD69, CD83, CD86 and MHC class II on B cells along with morphological transformation into plasmablasts and expression of CD27, CD38 and CD138. These effects are independent of adenosine. Mupadolimab binds to the N-terminal of CD73 in the closed position and competitively inhibits substrate binding. Mupadolimab enhanced antigen specific antibody response to SARS-CoV-2 spike protein and influenza hemagglutinin in humanized mouse models. Mupadolimab was evaluated as a monotherapy in a phase 1 trial ( NCT03454451 ) in 34 patients with advanced cancer and demonstrated binding to CD73 POS circulating cells and transient reduction in the number of B cells, with return of CD73 NEG B cells with memory phenotype. No dose-limiting toxicities or changes in serum immunoglobulins were seen. Conclusions Mupadolimab activates B cells and stimulates the production of antigen specific antibodies. The effects in patients with cancer suggest that activated, CD69 POS B cells redistribute to lymphoid tissues. Minor tumor regression was observed in several patients. These results support further investigation of mupadolimab as an immunotherapy for cancer and its potential use as a vaccine adjuvant. Trial registration number NCT03454451 .
Development of<sup>89</sup>Zr-anti-CD103 PET imaging for non-invasive assessment of cancer reactive T cell infiltration
Authors: Arjan Kol, Xiaoyu Fan, Marta A. Wazynska, Sander M.J. van Duijnhoven, Danique Giesen, Annechien Plat, Hans Van Eenennaam, Philip H. Elsinga, Hans W. Nijman, Marco de Bruyn
Journal: Journal for ImmunoTherapy of Cancer (2022)

Purpose CD103, an integrin specifically expressed on the surface of cancer-reactive T cells, is significantly increased during successful immunotherapy across human malignancies. In this study, we describe the generation and zirconium-89 ( 89 Zr) radiolabeling of monoclonal antibody (mAb) clones that specifically recognize human CD103 for non-invasive immune positron-emission tomography (PET) imaging of T cell infiltration as potential biomarker for effective anticancer immune responses. Experimental design First, to determine the feasibility of anti-CD103 immuno-PET to visualize CD103-positive cells at physiologically and clinically relevant target densities, we developed an 89 Zr-anti-murine CD103 PET tracer. Healthy, non-tumor bearing C57BL/6 mice underwent serial PET imaging after intravenous injection, followed by ex vivo biodistribution. Tracer specificity and macroscopic tissue distribution were studied using autoradiography combined with CD103 immunohistochemistry. Next, we generated and screened six unique mAbs that specifically target human CD103 positive cells. Optimal candidates were selected for 89 Zr-anti-human CD103 PET development. Nude mice (BALB/cOlaHsd-Foxn1nu) with established CD103 expressing Chinese hamster ovary (CHO) or CHO wild-type xenografts were injected with 89 Zr-anti-human CD103 mAbs and underwent serial PET imaging, followed by ex vivo biodistribution. Results 89 Zr-anti-murine CD103 PET imaging identified CD103-positive tissues at clinically relevant target densities. For human anti-human CD103 PET development two clones were selected based on strong binding to the CD103 + CD8 + T cell subpopulation in ovarian cancer tumor digests, non-overlapping binding epitopes and differential CD103 blocking properties. In vivo, both 89 Zr-anti-human CD103 tracers showed high target-to-background ratios, high target site selectivity and a high sensitivity in human CD103 positive xenografts. Conclusion CD103 immuno-PET tracers visualize CD103 T cells at relevant densities and are suitable for future non-invasive assessment of cancer reactive T cell infiltration.
Frontal and temporal coding dynamics in successive steps of complex behavior
Authors: Mikiko Kadohisa, Makoto Kusunoki, Daniel J. Mitchell, Cheshta Bhatia, Mark J. Buckley, John Duncan
Journal: Neuron (2022)

Ventrolateral prefrontal cortex (vlPFC), dorsolateral prefrontal cortex (dlPFC), and temporal cortex (TE) all contribute to visual decision-making. Accumulating evidence suggests that vlPFC may play a central role in multiple cognitive operations, perhaps resembling domain-general regions of the human frontal lobe. We trained monkeys in a task calling for learning, retrieval, and spatial selection of rewarded target objects. Recordings of neural activity covered large areas of vlPFC, dlPFC, and TE. Results suggested a central role for vlPFC in each cognitive operation with strong coding of each task feature, while only location was strongly coded in dlPFC and current object identity in TE. During target selection, target location was communicated first from vlPFC to dlPFC, followed by extensive mutual support. In vlPFC, stimulus identities were independently coded in different task operations. The results suggest a central role for the inferior frontal convexity in controlling successive operations of a complex, multi-step task.
Guideline-Discordant Care Among Direct-to-Consumer Testosterone Therapy Platforms
Authors: Justin M. Dubin, Erin Jesse, Richard J. Fantus, Nelson E. Bennett, Robert E. Brannigan, Nannan Thirumavalavan, Joshua A. Halpern
Journal: JAMA Internal Medicine (2022)

This cross-sectional study examines whether direct-to-consumer platforms provide guideline-concordant care regarding testosterone therapy.
The potential role of adherence factors in probiotic function in the gastrointestinal tract of adults and pediatrics: a narrative review of experimental and human studies
Authors: Frida Gorreja, W. Allan Walker
Journal: Gut Microbes (2022)

Numerous studies point to the important role of probiotic bacteria in gastrointestinal health. Probiotics act through mechanisms affecting enteric pathogens, epithelial barrier function, immune signaling, and conditioning of indigenous microbiota. Once administered, probiotics reach the gastrointestinal tract and interact with the host through bacterial surface molecules, here called adhesion factors, which are either strain- or specie-specific. Probiotic adhesion, through structural adhesion factors, is a mechanism that facilitates persistence within the gastrointestinal tract and triggers the initial host responses. Thus, an understanding of specific probiotic adhesion mechanisms could predict how specific probiotic strains elicit benefits and the potential of adherence factors as a proxy to predict probiotic function. This review summarizes the present understanding of probiotic adherence in the gastrointestinal tract. It highlights the bacterial adhesion structure types, their molecular communication with the host and the consequent impact on intestinal diseases in both adult and pediatric populations. Finally, we discuss knockout/isolation studies as direct evidence for adhesion factors conferring anti-inflammatory and pathogen inhibition properties to a probiotic.What is known: Probiotics can be used to treat clinical conditions.Probiotics improve dysbiosis and symptoms.Clinical trials may not confirm in vitro and animal studies.What is new: Adhesion structures may be important for probiotic function.Need to systematically determine physical characteristics of probiotics before selecting for clinical trials.Probiotics may be genetically engineered to add to clinical efficacy.
Vancomycin-resistant Enterococcus faecium: admission prevalence, sequence types and risk factors–a cross-sectional study in seven German university hospitals from 2014 to 2018
Authors: Anna M. Rohde, Sarah Walker, Michael Behnke, Simone Eisenbeis, Linda Falgenhauer, Jane C. Falgenhauer, Georg Häcker, Florian Hölzl, Can Imirzalioglu, Nadja Käding, Winfried V. Kern, Axel Kola, Evelyn Kramme, Alexander Mischnik, Silke Peter, Siegbert Rieg, Jan Rupp, Christian Schneider, Frank Schwab, Harald Seifert, Evelina Tacconelli, David Tobys, Janina Trauth, Anna Weber, Kyriaki Xanthopoulou, Janine Zweigner, Paul G. Higgins, Petra Gastmeier, Barisch Bader, Lena Biehl, Michael Buhl, Ariane Dinkelacker, Moritz Fritzenwanker, Hanna Gölz, Catriona Hennelly, Susanne Herold, Azita Lengler, Dana Lenke, Gabriele Peyerl-Hoffmann, Luis Alberto Peña Diaz, Georg Pilarski, Susanna Proske, Judith Schmiedel, Heike Spitznagel, Katrin Spohn, Norbert Thoma, Martina Vavra, Thorsten Wille, Maria J.G.T. Vehreschild
Journal: Clinical Microbiology and Infection (2022)
Ethnic differences in hypertension management, medication use and blood pressure control in UK primary care, 2006–2019: a retrospective cohort study
Authors: Sophie V. Eastwood, Alun D. Hughes, Laurie Tomlinson, Rohini Mathur, Liam Smeeth, Krishnan Bhaskaran, Nishi Chaturvedi
Journal: The Lancet Regional Health - Europe (2022)

In the UK, previous work suggests ethnic inequalities in hypertension management. We studied ethnic differences in hypertension management and their contribution to blood pressure (BP) control.We conducted a cohort study of antihypertensive-naïve individuals of European, South Asian and African/African Caribbean ethnicity with a new raised BP reading in UK primary care from 2006 to 2019, using the Clinical Practice Research Datalink (CPRD). We studied differences in: BP re-measurement after an initial hypertensive BP, antihypertensive initiation, BP monitoring, antihypertensive intensification, antihypertensive persistence/adherence and BP control one year after antihypertensive initiation. Models adjusted for socio-demographics, BP, comorbidity, healthcare usage and polypharmacy (plus antihypertensive class, BP monitoring, intensification, persistence and adherence for BP control models).A total of 731,506 (93.5%), 30,379 (3.9%) and 20,256 (2.6%) people of European, South Asian and African/African Caribbean ethnicity were studied. Hypertension management indicators were similar or more favourable for South Asian than European groups (OR/HR [95% CI] in fully-adjusted models of BP re-measurement: 1.16 [1.09, 1.24]), antihypertensive initiation: 1.49 [1.37, 1.62], BP monitoring: 0.97 [0.94, 1.00] and antihypertensive intensification: 1.10 [1.04, 1.16]). For people of African/African Caribbean ethnicity, BP re-measurement rates were similar to those of European ethnicity (0.98 [0.91, 1.05]), and antihypertensive initiation rates greater (1.48 [1.32, 1.66]), but BP monitoring (0.91 [0.87, 0.95]) and intensification rates lower (0.93 [0.87, 1.00]). Persistence and adherence were lower in South Asian (0.48 [0.45, 0.51] and 0.51 [0.47, 0.56]) and African/African Caribbean (0.38 [0.35, 0.42] and 0.39 [0.36, 0.43]) than European groups. BP control was similar in South Asian and less likely in African/African Caribbean than European groups (0.98 [0.90, 1.06] and 0.81 [0.74, 0.89] in age, gender and BP adjusted models). The latter difference attenuated after adjustment for persistence (0.91 [0.82, 0.99]) or adherence (0.92 [0.83, 1.01]), and was absent for antihypertensive-adherent people (0.99 [0.88, 1.10]).We demonstrate that antihypertensive initiation does not vary by ethnicity, but subsequent BP control was notably lower among people of African/African Caribbean ethnicity, potentially associated with being less likely to remain on regular treatment. A nationwide strategy to understand and address differences in ongoing management of people on antihypertensives is imperative.Diabetes UK.
Comparing the efficacy of mindfulness-based therapy and cognitive-behavioral therapy for depression in head-to-head randomized controlled trials: A systematic review and meta-analysis of equivalence
Authors: Kristine Trettø Sverre, Eva Rames Nissen, Ingeborg Farver-Vestergaard, Maja Johannsen, Robert Zachariae
Journal: Clinical Psychology Review (2022)

While Cognitive Behavioral Therapy (CBT) is recommended as first-line treatment for depression, a significant minority do not show an adequate treatment response. Despite evidence for the efficacy of Mindfulness-Based Therapies (MBT) both in treating current depression and preventing relapse, it remains unknown whether MBT and CBT are equivalent in the treatment of current depression.Five databases were searched for randomized controlled trials (RCTs) directly comparing MBT with CBT and including depression as primary or secondary outcome.When pooling the results of 30 independent RCTs with a total of 2750 participants, MBT and CBT were statistically significantly equivalent at both post-intervention (Hedges's g = -0.009; p < .001) and follow-up (g = -0.033; p = .001). Supplementary Bayesian analyses provided further support for the alternative hypothesis of no difference between MBT and CBT. When exploring possible sources of heterogeneity, the differences at follow-up were smaller between CBT and mindfulness-based cognitive therapy (MBCT) than between CBT and mindfulness-based stress-reduction (MBSR) (Slope = 0.37;p = .022).The currently available evidence suggests that that MBT and CBT are equally efficacious in treating current adult depression. It remains unclear whether the similar effects of the two intervention types are due to different mechanisms or common factors.
Increased FDG Uptake in Skin Rashes Caused by EGFR Inhibitors
Authors: Özge Erol Fenercioğlu, Merve Cin, Ediz Beyhan, Rahime Şahin, Tevfik Fikret Çermik
Journal: Clinical Nuclear Medicine (2022)

Most patients treated with epidermal growth factor receptor inhibitors develop cutaneous advance effects. The extent and severity of treatment-related skin rashes are associated with good treatment response and prognosis. Herein, we presented increased uptake of the 18F-FDG in skin rashes after treatment with epidermal growth factor receptor inhibitors in 2 patients diagnosed with metastatic colorectal cancer.
Solitary Scapular Metastasis as the First Presentation of Prostate Adenocarcinoma Identified on 99mTc-MDP SPECT/CT
Authors: Wei Liu, Xiao-Zuo Zheng, Zi-Qian Dong, Jian-Min Huang, Peng Xie
Journal: Clinical Nuclear Medicine (2022)

Metastases of prostate carcinoma in the skeleton are usually multiple. Solitary metastasis in appendicular skeleton is extremely rare. We present bone scan findings of solitary scapular metastasis from prostate adenocarcinoma as the initial presentation of his malignancy in a 62-year-old man. The 99mTc-MDP SPECT/CT demonstrated intense activity in the coracoid process of left scapula, whereas the tracer uptakes in other bones were not typical of metastases. The subsequent pathological results of the punctured left scapula confirmed as metastasis from prostate adenocarcinoma.
18F-FDG PET/CT in Primary Mesothelioma of the Liver
Authors: Birgit Pernthaler, Luka Brcic, Reingard Maria Aigner, Michael Fuchsjäger, Emina Talakic
Journal: Clinical Nuclear Medicine (2022)

Primary malignant mesothelioma is a rarity among malignant liver tumors. We present the case of a 48-year-old woman presenting with increasing upper abdominal discomfort and inappetence accompanied by a weight loss of approximately 10 kg. CT and MRI revealed a highly suspicious mass lesion in the liver. 18F-FDG PET/CT performed for staging showed a pathological 18F-FDG uptake of the known liver tumor. Histology and immunohistochemistry indicated mesothelioma of the liver. Herein we present a rare case of primary mesothelioma in the liver with CT, MRI, and 18F-FDG PET/CT.
Metastatic Papillary Thyroid Cancer Mimicking Hypopharyngeal Carcinoma
Authors: Bulin Du, Shu Wang, Yi Liu, Yaming Li, Xuena Li
Journal: Clinical Nuclear Medicine (2022)

Papillary thyroid cancer (PTC) metastasizing to the hypopharynx is extremely rare. Here, we describe FDG PET/CT findings of lesions in the posterior hypopharyngeal wall and left parapharyngeal space in a 58-year-old man who complained of blood in the sputum. The patient had a history of postoperative PTC. Therefore, hypopharyngeal carcinoma with lymph node metastasis was suspected. However, metastasis of PTC was pathologically confirmed after surgery. Hypopharyngeal metastasis of PTC is rare, which should be differentiated from hypopharyngeal carcinoma with metastasis.
Increased 18F-FAPI PET/CT Uptake in a Case of Brucellosis of Lumbar Vertebral Body
Authors: Xingyu Mu, Zhuohao Zhu, Wei Fu
Journal: Clinical Nuclear Medicine (2022)

Vertebral brucellosis is a relatively rare disease that usually emerges in animal husbandry areas. We report a case that brucellosis of lumbar vertebral body showed an intense uptake of FAPI on 18F-FAPI PET/CT, which mimics to malignant lesions or vertebral tuberculosis. It is an interesting finding to realize that vertebral brucellosis is also one of the reasons for intense uptake of FAPI.
Isolated Urinary Bladder Metastasis in Renal Cell Carcinoma Detected on 18F-FDG PET/CT Scan
Authors: Sudip Dey, Gadde Sathya Sunil, Ritu Verma, Ethel Shangne Belho, Babita Drolia, Sunila Jain, Nitin Gupta
Journal: Clinical Nuclear Medicine (2022)

Renal cell carcinoma (RCC) is an aggressive carcinoma with hematogenous spread commonly to lungs, liver, and bones. However, few cases of isolated urinary bladder metastasis have also been reported. Here we report a case of 63-year-old man, a known case of left RCC (clear cell type), post left nephrectomy, who was on regular clinicoradiological follow-up. He presented with complaints of painless hematuria; on further evaluation, 18F-FDG PET/CT revealed few FDG-avid intramural nodular lesions along the walls of urinary bladder. He underwent TURBT, and the tissue was sent for histopathological examination, which was diagnostic of metastatic RCC.
Abstract 10464: In-Hospital and Long-Term Impact of Right and Left Bundle-Branch Block in Mortality in Patients With Acute Myocardial Infarction
Authors: Jose C Nicolau, Adriadne Bertolin, Marcela Juliasz, FELIPE CHIU, Luciano Baracioli, Felipe Lima, Roberto R Giraldez, Cesar Pereira, Maria Andrade, Andre Ribeiro, Nádia Quintanilha, Glaylton Santos, Cristhian V Espinoza, Remo Furtado
Journal: Circulation (2022)

Introduction: There are scarce data in the literature analyzing, in patients with acute myocardial infarction (AMI), the impact of right (RBBB) and left bundle-branch block (LBBB) on mortality, especially in the long-run after hospital discharge. Hypothesis: RBBB and LBBB is associated with in-hospital and long-term mortality in patients with AMI. Methods: Retrospective analysis from an administrative databank of patients (pts) with acute coronary syndromes, collected prospectively between 1998 and 2016. From a total of 6466 pts, we selected 2895 with AMI (72% men, mean age 63.7 years, 50% with ST-segment-elevation AMI) and complete follow-up for up to 17 years (mean 5.5 years). In-hospital and long-term mortality was compared with RBBB (incidence=5.8%) and LBBB (incidence=3.9%) in models unadjusted and adjusted for 14 variables including age, type/location of AMI and in-hospital cardiogenic shock. Results: In-hospital mortality was 15.5% vs. 7.0% for pts with or without RBBB, respectively (OR=2.41, P&lt;0.001; adj. OR=1.32, 0.37); for pts with of without LBBB the percentages were 14.2% vs. 7.3%, respectively (OR=2.10, P=0.008, adj. OR=1.13, P=0.74). The results for the long-term follow-up are depicted in the figure. Conclusions: After adjustments, there was no association between RBBB or LBBB with higher in-hospital death among patients with AMI. On the other hand, in the long-term follow-up LBBB, but not RBBB, showed significant and independent association with higher mortality.
68Ga-DOTANOC PET/CT in Adrenal Schwannoma
Authors: Piyush Aggarwal, Harmandeep Singh, Rajender Kumar, Ritambhra Nada, Girdhar S. Bora, Rama Walia
Journal: Clinical Nuclear Medicine (2022)

Abstract Adrenal schwannoma is a rare adrenal incidentaloma. It is a benign tumor arising from the Schwann cells. Differentiating benign from malignant adrenal lesions requires a combination of clinical, biochemical, imaging, and histopathological findings. 68 Ga-DOTANOC PET/CT is one of the sensitive imaging modalities to detect adrenal lesions such as pheochromocytoma. Multiple benign and malignant lesions show somatostatin receptor expression causing a high probability of false-positive findings on somatostatin receptor imaging. We present a case of adrenal incidentaloma positive on 68 Ga-DOTANOC PET, which revealed a benign adrenal spindle cell tumor on histopathology.
Potential Role of 68Ga-NOTA-Duramycin PET/CT Imaging for Early Response Evaluation in a Lymphoma Patient
Authors: Gurvinder Kaur, Jaya Shukla, Ashwani Sood, Gaurav Prakash, Venkata Subramanian Krishnaraju, Nivedita Rana, Somit Pandey, Harmandeep Singh, Rajender Kumar, Amanjit Bal, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2022)

Abstract Duramycin, a 19 amino acids peptide, is known for its potential to target phosphatidylethanolamine. During cell death (apoptosis), rearrangement of membrane phospholipids results in the externalization of phosphatidylethanolamine to the outer leaflet of the cell membrane, which can be imaged using 68 Ga-NOTA-duramycin. We report 68 Ga-NOTA-duramycin imaging in a 50-year-old man with biopsy-proven diffuse large B-cell lymphoma planned for anthracycline-based chemotherapy. 68 Ga-NOTA-duramycin PET/CT imaging along with 18 F-FDG PET/CT was performed before and after 2 cycles of chemotherapy. The tracer avidity in interim 68 Ga-NOTA-duramycin PET/CT showed its diagnostic potential to assess early response to chemotherapy.